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Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria (MIM)

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ClinicalTrials.gov Identifier: NCT02614404
Recruitment Status : Completed
First Posted : November 25, 2015
Last Update Posted : February 11, 2021
Sponsor:
Collaborators:
Purdue University
University of Turin, Italy
Università degli Studi di Sassari
Hue University
Information provided by (Responsible Party):
HuLow

Brief Summary:
The purpose of this study is to determine the efficacy and safety of imatinib in combination with dihydroartemisinin plus piperaquine in the treatment uncomplicated P. falciparum malaria in adult male patients.

Condition or disease Intervention/treatment Phase
Plasmodium Falciparum Malaria Drug: Imatinib combination therapy Drug: Dihydroartemisinin-piperaquine Phase 1

Detailed Description:
An exploratory study to examine the efficacy and safety of imatinib mesylate in combination with dihydroartemisinin plus piperaquine on suppression of parasitemia in patients with uncomplicated Plasmodium falciparum malaria. In vitro studies of P. falciparum parasitized erythrocytes demonstrate that inhibitors of the protein tyrosine kinase SYK prevent malaria parasite egress from infected red blood cells and thereby terminate the parasite's life cycle. Although no potent syk kinase inhibitors were approved for human use at the time of initiation of this study, a bcr-abl tyrosine kinase inhibitor (imatinib mesylate (Gleevec®)) that also exhibits off-target inhibition of syk tyrosine kinase, has been FDA-approved for treatment of a number of human malignancies including chronic myelogenous leukemia and GIST. Because imatinib can be taken daily for many years without significant toxicity, it can be used to obtain a preliminary indication of whether inhibition of erythrocyte syk kinase can suppress parasitemia in patients with P. falciparum malaria. In a phase 1 clinical trial on the same patient population, anti-malaria activity was observed with imatinib, with little or no accompanying toxicity. Because dihydroartemisinin plus piperaquine constitute the currently used standard-of-care therapy for malaria in Southeast Asia, the above trial will test the safety and efficacy of the combination of imatinib plus dihydroartemisinin and piperaquine in treatment of uncomplicated malaria. In this pilot study, the rate of decrease in peripheral blood parasitemia in 30 adult male patients with uncomplicated malaria will be compared to the same rate of decrease in parasitemia in 30 adult male patients treated solely with dihydroartemisinin plus piperaquine.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 15 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Effect of Imatinib on Suppression of Malaria Parasites in Patients With Uncomplicated Plasmodium Falciparum Malaria
Actual Study Start Date : November 2015
Actual Primary Completion Date : December 2, 2016
Actual Study Completion Date : February 2, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Malaria

Arm Intervention/treatment
Experimental: Imatinib combination therapy
Administration of imatinib (400 mg/day) plus dihydroartemisinin (40 mg/day) plus piperaquine (320 mg/day) to uncomplicated adult male malaria patients. Normal health parameters will be monitored continuously to evaluate safety and the decrease in peripheral blood parasitemia with time will be quantitated to assess efficacy.
Drug: Imatinib combination therapy
Imatinib plus dihydroartemisinin plus piperaquine
Other Names:
  • Gleevec
  • Glivec

Active Comparator: dihydroartemisinin plus piperaquine
Administration of dihydroartemisinin (40 mg/day) plus piperaquine (320 mg/day) to uncomplicated adult male malaria patients. Normal health parameters will be monitored continuously to evaluate safety and the decrease in peripheral blood parasitemia with time will be quantitated to assess efficacy.
Drug: Dihydroartemisinin-piperaquine
Standard of care
Other Names:
  • Artekin
  • Eurartesim
  • Diphos
  • Timequin
  • Duocotecxin
  • Malacur
  • Ridmal




Primary Outcome Measures :
  1. Time to Parasite Clearance [ Time Frame: From baseline to the time point when the blood parasite count is zero (up to a maximum of 5 days) ]
    Parasite clearance was determined by assessing the parasite count in blood, using thin film, thick film and qPCR analysis

  2. 28-day Cure Rate [ Time Frame: Day 28 ]
    28-day cure rate was defined as the percentage of participants with blood parasite count of zero after 28 days of treatment and no evidence of recurrent infection with the same parasite genotype after reduction of the asexual parasitemia. Follow up after treatment will only be performed in the case of complete clearance of parasites at D5 due to Imatinib treatment.


Secondary Outcome Measures :
  1. Frequency of adverse events [ Time Frame: Within 1 week of beginning treatment with imatinib ]

    Adverse events (AEs) are defined as events possibly related to the study drug as judged by physician that occur within 1 week of beginning treatment with imatinib.

    1. Incidence, severity, drug-relatedness, seriousness of adverse events
    2. Laboratory values (biochemistry and haematology)
    3. Vital signs



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Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Gender: only adults are selected for the trial; note that female subjects cannot be women of child-bearing age.
  • Age: 18-50 years.
  • Target disease: Uncomplicated Plasmodium falciparum malaria

Exclusion Criteria:

  • symptoms and signs of complicated malaria
  • including continuous high fever of over 390C, psychiatric disorders, confusion, other neurological symptoms, symptoms and signs of functional impairment of the organs such as lungs, kidneys or cardiovascular system;
  • symptoms and signs of liver damage or kidney damage
  • symptoms and signs of another complicating infection such as pneumonia, dengue fever, and other bacterial infection.
  • P. falciparum > 25.000 / mm3
  • WBC <4000 and >10.000 /mm3

    • RBC < 3.5x106/mm3
    • Platelets < 40.000 /mm3
  • Hemoglobin < 10 g/dL
  • ALT more than 200% of the upper limit (56 units/L)
  • AST more than 200% of the upper limit (40 units/L)
  • Blood creatine more than 75% of the upper limit (men: 1.2 mg/dL, women 1 mgdL)
  • Serum total protein < 6 g/L
  • Glycemia < 50 mg/dL> 200 mg/dL
  • Standard urine test Serious alterations
  • Concomitant treatments

Antimalarial Drugs Anticoagulant therapy


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02614404


Locations
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Vietnam
A Tuc
Huong Hoa, Quang Tri, Vietnam, 520000
Sponsors and Collaborators
HuLow
Purdue University
University of Turin, Italy
Università degli Studi di Sassari
Hue University
Investigators
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Principal Investigator: Huynh D Chien, MD, PhD Hue University
Principal Investigator: Francesco M Turrini, MD, PhD University of Turin, Italy
Principal Investigator: Philip S Low, PhD Purdue University
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Responsible Party: HuLow
ClinicalTrials.gov Identifier: NCT02614404    
Other Study ID Numbers: HuLow-201605
First Posted: November 25, 2015    Key Record Dates
Last Update Posted: February 11, 2021
Last Verified: February 2021
Keywords provided by HuLow:
Plasmodium falciparum
Uncomplicated malarial
imatinib mesylate
antimalarials
Additional relevant MeSH terms:
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Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Infections
Vector Borne Diseases
Piperaquine
Artenimol
Imatinib Mesylate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimalarials
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents